The Repellent Capacity against Sitophilus zeamais (Coleoptera: Curculionidae) and In Vitro Inhibition of the Acetylcholinesterase Enzyme of 11 Essential Oils from Six Plants of the Caribbean Region of Colombia.

The repellent capacity against Sitophilus zeamais and the in vitro inhibition on AChE of 11 essential oils, isolated from six plants of the northern region of Colombia, were assessed using a modified tunnel-type device and the Ellman colorimetric method, respectively. The results were as follows: (i) the degree of repellency (DR) of the EOs against S. zeamais was 20-68% (2 h) and 28-74% (4 h); (ii) the IC50 values on AChE were 5-36 µg/mL; likewise, the %inh. on AChE (1 µg/cm3 per EO) did not show any effect in 91% of the EO tested; (iii) six EOs (Bursera graveolens-bark, B. graveolens-leaves, B. simaruba-bark, Peperomia pellucida-leaves, Piper holtonii (1b*)-leaves, and P. reticulatum-leaves) exhibited a DR (53-74%) ≥ C+ (chlorpyrifos-61%), while all EOs were less active (8-60-fold) on AChE compared to chlorpyrifos (IC50 of 0.59 µg/mL). Based on the ANOVA/linear regression and multivariate analysis of data, some differences/similarities could be established, as well as identifying the most active EOs (five: B. simaruba-bark, Pep. Pellucida-leaves, P. holtonii (1b*)-leaves, B. graveolens-bark, and B. graveolens-leaves). Finally, these EOs were constituted by spathulenol (24%)/ß-selinene (18%)/caryophyllene oxide (10%)-B. simaruba; carotol (44%)/dillapiole (21%)-Pep. pellucida; dillapiole (81% confirmed by 1H-/13C-NMR)-P. holtonii; mint furanone derivative (14%)/mint furanone (14%)-B. graveolens-bark; limonene (17%)/carvone (10%)-B. graveolens-leaves.

Antithrombotic therapy-A simple algorithm for the interventional pathologist: A case series.

We can safely manage patients on antithrombotic therapy in the interventional pathology practice with this practical algorithm based on the new Antithrombotic Therapy Management Guidelines. This new algorithm helps ensure safe care for patients on antithrombotic therapy undergoing interventional pathology procedures. #interventionalpathology.

Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.

Sepsis and septic shock are associated with high mortality, with diagnosis and treatment remaining a challenge for clinicians. Their management classically encompasses hemodynamic resuscitation, antibiotic treatment, life support, and focus control; however, there are aspects that have changed. This narrative review highlights current and avant-garde methods of handling patients experiencing septic shock based on the experience of its authors and the best available evidence in a context of uncertainty. Following the first recommendation of the Surviving Sepsis Campaign guidelines, it is recommended that specific sepsis care performance improvement programs are implemented in hospitals, i.e., "Sepsis Code" programs, designed ad hoc, to achieve this goal. Regarding hemodynamics, the importance of perfusion and hemodynamic coherence stand out, which allow for the recognition of different phenotypes, determination of the ideal time for commencing vasopressor treatment, and the appropriate fluid therapy dosage. At present, this is not only important for the initial timing, but also for de-resuscitation, which involves the early weaning of support therapies, directed elimination of fluids, and fluid tolerance concept. Finally, regarding blood purification therapies, those aimed at eliminating endotoxins and cytokines are attractive in the early management of patients in septic shock.

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.

Single-cell transcriptomic analysis of renal allograft rejection reveals insights into intragraft TCR clonality.

Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked cellular context critical to mechanistic understanding of how rejection occurs despite immunosuppression (IS). We performed combined single-cell RNA transcriptomic and TCR-α/ß sequencing on rBx from patients with ACR under differing IS drugs: tacrolimus, iscalimab, and belatacept. We found distinct CD8+ T cell phenotypes (e.g., effector, memory, exhausted) depending upon IS type, particularly within expanded CD8+ T cell clonotypes (CD8EXP). Gene expression of CD8EXP identified therapeutic targets that were influenced by IS type. TCR analysis revealed a highly restricted number of CD8EXP, independent of HLA mismatch or IS type. Subcloning of TCR-α/ß cDNAs from CD8EXP into Jurkat 76 cells (TCR-/-) conferred alloreactivity by mixed lymphocyte reaction. Analysis of sequential rBx samples revealed persistence of CD8EXP that decreased, but were not eliminated, after successful antirejection therapy. In contrast, CD8EXP were maintained in treatment-refractory rejection. Finally, most rBx-derived CD8EXP were also observed in matching urine samples, providing precedent for using urine-derived CD8EXP as a surrogate for those found in the rejecting allograft. Overall, our data define the clonal CD8+ T cell response to ACR, paving the next steps for improving detection, assessment, and treatment of rejection.

In-hospital cardiac arrest: Incidence, prognostic factors and results.

BACKGROUND AND AIMS: In-hospital cardiac arrest (CA) is a clinical entity with high morbidity and mortality that occurs in up to 2% of hospitalized patients. It is a public health problem with important economic, social, and medical repercussions, and as such its incidence needs to be reviewed and improved. The aim of this study was to determine the incidence of in-hospital CA, return of spontaneous circulation (ROSC), and survival rates at Hospital de la Princesa, and to define the clinical and demographic characteristics of patients with in-hospital CA. PATIENTS AND METHODS: Retrospective observational chart review of patients presenting in-hospital CA and treated by anaesthesiologists from the hospital's rapid intervention team. Data were collected over 1 year. RESULTS: Forty four patients were included in the study, of which 22 (50%) were women. Mean age was 75.7 years (±15.78 years), and incidence of in-hospital CA was 2.88 per 100,000 hospital admissions. Twenty two patients (50%) achieved ROSC and 11 patients (25%) survived until discharge home. The most prevalent comorbidity was arterial hypertension (63.64%); 66.7% of cases were not witnessed, and only 15.9% presented a shockable rhythm. CONCLUSIONS: These results are similar to those reported in other larger studies. We recommend introducing immediate intervention teams and devoting time to training hospital staff in in-hospital CA.

Single cell transcriptomic analysis of renal allograft rejection reveals novel insights into intragraft TCR clonality.

Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked cellular context critical to mechanistic understanding. We performed combined single cell RNA transcriptomic and TCRα/ß sequencing on rBx from patients with ACR under differing immunosuppression (IS): tacrolimus, iscalimab, and belatacept. TCR analysis revealed a highly restricted CD8 + T cell clonal expansion (CD8 EXP ), independent of HLA mismatch or IS type. Subcloning of TCRα/ß cDNAs from CD8 EXP into Jurkat76 cells (TCR -/- ) conferred alloreactivity by mixed lymphocyte reaction. scRNAseq analysis of CD8 EXP revealed effector, memory, and exhausted phenotypes that were influenced by IS type. Successful anti-rejection treatment decreased, but did not eliminate, CD8 EXP , while CD8 EXP were maintained during treatment-refractory rejection. Finally, most rBx-derived CD8 EXP were also observed in matching urine samples. Overall, our data define the clonal CD8 + T cell response to ACR, providing novel insights to improve detection, assessment, and treatment of rejection.

Synchronous colorectal cancer and abdominal aortic aneurysm treated simultaneously. Is a one-stage surgery a feasible treatment?

The finding of synchronous abdominal aortic aneurysm and colorectal cancer is rare. There is no consensus on which is the best surgical approach, so its management remains uncertain. A 64-year-old man was diagnosed with synchronous abdominal aortic aneurysm and rectal cancer. One-stage treatment was performed: He underwent endovascular aortic repair followed by simultaneous laparoscopic tumor resection. In our experience, one-stage minimally invasive surgery could be a safe and feasible treatment for concomitant abdominal aortic aneurysm and colorectal cancer.

A class-mismatched TCR bypasses MHC restriction via an unorthodox but fully functional binding geometry.

MHC restriction, which describes the binding of TCRs from CD4+ T cells to class II MHC proteins and TCRs from CD8+ T cells to class I MHC proteins, is a hallmark of immunology. Seemingly rare TCRs that break this paradigm exist, but mechanistic insight into their behavior is lacking. TIL1383I is a prototypical class-mismatched TCR, cloned from a CD4+ T cell but recognizing the tyrosinase tumor antigen presented by the class I MHC HLA-A2 in a fully functional manner. Here we find that TIL1383I binds this class I target with a highly atypical geometry. Despite unorthodox binding, TCR signaling, antigen specificity, and the ability to use CD8 are maintained. Structurally, a key feature of TIL1383I is an exceptionally long CDR3ß loop that mediates functions that are traditionally performed separately by hypervariable and germline loops in canonical TCR structures. Our findings thus expand the range of known TCR binding geometries compatible with normal function and specificity, provide insight into the determinants of MHC restriction, and may help guide TCR selection and engineering for immunotherapy.

WiFi FTM and UWB Characterization for Localization in Construction Sites.

A high-precision location is becoming a necessity in the future Industry 4.0 applications that will come up in the near future. However, the construction sector remains particularly obsolete in the adoption of Industry 4.0 applications. In this work, we study the accuracy and penetration capacity of two technologies that are expected to deal with future high-precision location services, such as ultra-wide band (UWB) and WiFi fine time measurement (FTM). For this, a measurement campaign has been performed in a construction environment, where UWB and WiFi-FTM setups have been deployed. The performance of UWB and WiFi-FTM have been compared with a prior set of indoors measurements. UWB seems to provide better ranging estimation in LOS conditions but it seems cancelled by reinforcement concrete for propagation and WiFi is able to take advantage of holes in the structure to provide location services. Moreover, the impact of fusion of location technologies has been assessed to measure the potential improvements in the construction scenario.

Early and late results of open surgical and endovascular treatment of infrarenal abdominal aortic aneurysms, selected according to surgical risk.

BACKGROUND: Open surgical repair (OSR) and endovascular aneurysm repair (EVAR) surgery are alternative treatments for infrarenal abdominal aortic aneurysm (IRAAA). OBJECTIVES: To compare OSR and EVAR for the treatment of IRAAA. METHODS: 119 patients with IRAAA were electively operated by the same surgeon between January 1, 2006 and December 31, 2015, following selection for OSR or EVAR according to surgical risk. Complications, reinterventions, failures, and early and late mortality were analyzed. RESULTS: 63 OSR and 56 EVAR patients were analyzed. They were similar in terms of age (70 years), gender (92% men), and average diameter of IRAAA (6.5 cm), but with different comorbidities, surgical risk, and anatomy. EVAR was better than OSR regarding time in the operating theatre (177.5 vs. 233.3 minutes), need for transfusion (25 vs. 73%), and length of stay in ICU (1.3 vs. 3.3 days) and hospital (8.1 vs. 11.1 days). OSR allowed more associated procedures to be conducted simultaneously (19.0 vs. 1.8%). There were no significant differences between the groups with respect to complications (25.4 vs. 25.1%), reinterventions (3.2 vs. 5.2%), or early mortality (1.6 vs. 0%). During follow-up, OSR was associated with fewer revisions (3.13 vs. 4.21), angio-CTs (0.22 vs. 3.23), complications (6.4 vs. 37.5%), reinterventions (3.2 vs. 23.2%), and failures (1.6 vs. 10.7%), and had better survival (78.2 vs. 63.2%). CONCLUSIONS: Correct selection of patients achieves excellent results because it avoids OSR in patients at high risk and avoids EVAR in patients with high anatomical complexity, achieving similar results in the perioperative period, but better results for OSR over the course of follow-up.

CONTEXTO: A cirurgia aberta (CA) e o reparo endovascular de aneurisma (REVA) são tratamentos alternativos para o aneurisma da aorta abdominal infrarrenal (AAAIR). OBJETIVOS: Comparar CA e REVA no tratamento do AAAIR. MÉTODOS: Foram incluídos 119 pacientes com AAAIR, operados eletivamente pelo mesmo cirurgião entre 1 de janeiro de 2006 e 31 de dezembro de 2015, após seleção para CA ou REVA de acordo com o risco cirúrgico. Complicações, reintervenções, falhas e mortalidade precoce e tardia foram analisadas. RESULTADOS: Foram analisados 63 pacientes de CA e 56 de REVA, com semelhanças de idade (70 anos), sexo (92% homens) e diâmetro médio do AAAIR (6,5 cm), mas com diferentes comorbidades, riscos cirúrgicos e anatomias. O REVA foi melhor que a CA em relação ao tempo na sala de cirurgia (177,5 vs. 233,3 minutos), necessidade de transfusão (25 vs. 73%) e tempo de permanência na unidade de terapia intensiva (1,3 vs. 3,3 dias) e no hospital (8,1 vs. 11,1 dias). A CA permitiu que mais procedimentos associados fossem realizados simultaneamente (19,0 vs. 1,8%). Não houve diferenças significativas entre os grupos em relação a complicações (25,4 vs. 25,1%), reintervenções (3,2 vs. 5,2%) e mortalidade precoce (1,6 vs. 0%). Durante o acompanhamento, a CA apresentou menos revisões (3,13 vs. 4,21), angiotomografias (0,22 vs. 3,23), complicações (6,4 vs. 37,5%), reintervenções (3,2 vs. 23,2%) e falhas (1,6 vs. 10,7%), além de ter melhor sobrevida (78,2 vs. 63,2%). CONCLUSÕES: A seleção correta dos pacientes proporciona excelentes resultados porque evita pacientes com alto risco para CA e com complexidade anatômica para REVA. Os resultados são semelhantes no período perioperatório, mas melhores para CA durante o acompanhamento.

Meningioma como causa poco común de hiposmia. A propósito de un caso

Resumen La afectación del sentido del olfato puede pasar desapercibida en gran parte de los pacientes, siendo únicamente valorada cuando la alteración es importante. Sin embargo, la hiposmia es un síntoma asociado a numerosas patologías, de menor a mayor gravedad. Este sentido está relacionado con nuestros recuerdos y puede alertarnos de potenciales amenazas. Como médicos especialistas en Otorrinolaringología debemos estar alerta ante determinados síntomas que orienten a posible etiología central. Presentamos el caso de una mujer de 39 años que acudió al Servicio de Otorrinolaringología del Hospital General Universitario Morales Meseguer derivada por hiposmia de un año de evolución con cervicalgia y cefalea occipital progresiva, sin otra sintomatología asociada. La exploración otorrinolaringológica resultó normal. Debido a la persistencia sintomática se solicitó una tomografía computarizada de senos paranasales con hallazgos de masa intracraneal extraaxial compatible con meningioma de fosa craneal anterior.

Abstract The affectation of smell can go unnoticed in a great part of the patients, being only valued when the alteration is important. However, this sense is related to our memories and can alert us to potential threats. As otolaryngologists we must be alert to certain symptoms that may lead to a possible central aetiology. We present the case of a 39-year-old woman who went to the otolaryngology service at Morales Meseguer General University Hospital due to one-year evolution of hyposmia with cervicalgia and progressive occipital headache, with no other symptoms associated. The otolaryngology examination was anodyne. In view of symptomatic persistence, a paranasal sinus computed tomography scan was requested with findings of extra-axial intracranial mass compatible with anterior cranial fossa meningioma.

Direct Powder Extrusion of Paracetamol Loaded Mixtures for 3D Printed Pharmaceutics for Personalized Medicine via Low Temperature Thermal Processing.

Three-dimensional printed drug development is nowadays an active area in the pharmaceutical industry, where the search for an appropriate edible carrier that permits the thermal processing of the mixture at temperature levels that are safe for the drug is an important field of study. Here, potato starch and hydroxypropyl cellulose based mixtures loaded with paracetamol up to 50% in weight were processed by hot melt extrusion at 85 °C to test their suitability to be thermally processed. The extruded mixtures were tested by liquid chromatography to analyze their release curves and were thermally characterized. The drug recovery was observed to be highly dependent on the initial moisture level of the mixture, the samples being prepared with an addition of water at a ratio of 3% in weight proportional to the starch amount, highly soluble and easy to extrude. The release curves showed a slow and steady drug liberation compared to a commercially available paracetamol tablet, reaching the 100% of recovery at 60 min. The samples aged for 6 weeks showed slower drug release curves compared to fresh samples, this effect being attributable to the loss of moisture. The paracetamol loaded mixture in powder form was used to print pills with different sizes and geometries in a fused deposition modelling three-dimensional printer modified with a commercially available powder extrusion head, showing the potential of this formulation for use in personalized medicine.

Tumor rejection properties of gp100209-specific T cells correlate with T cell receptor binding affinity towards the wild type rather than anchor-modified antigen.

Although there are exceptions and outliers, T cell functional responses generally correlate with the affinity of a TCR for a peptide/MHC complex. In one recently described outlier case, the most promising clinical candidate in a series of TCRs specific for the gp100209 melanoma antigen bound with the weakest solution affinity and produced the least amount of cytokine in vitro. Hypotheses for this outlier behavior included unusual cytokine expression patterns arising from an atypical TCR binding geometry. Studying this instance in more detail, we found here that outlier behavior is attributable not to unusual cytokine patterns or TCR binding, but the use of a position 2 anchor-modified peptide variant in in vitro experiments instead of the wild type antigen that is present in vivo. Although the anchor-modified variant has been widely used in basic and clinical immunology as a surrogate for the wild type peptide, prior work has shown that TCRs can clearly distinguish between the two. We show that when this differential recognition is accounted for, the functional properties of gp100209-specific TCRs track with their affinity towards the peptide/MHC complex. Beyond demonstrating the correlates with T cell function for a clinically relevant TCR, our results provide important considerations for selection of TCRs for immunotherapy and the use of modified peptides in immunology.

Gestión de la consulta de otorrinolaringología durante el estado de alarma por la pandemia del COVID-19. ¿Es útil la consulta telefónica en ORL? / Management of the ENT consultation during the COVID-19 pandemic alert. Are ENT telephone consultations useful?

Objetivo: Describir cómo se gestionaron las consultas de los servicios de Otorrinolaringología y Cirugía de Cabeza y Cuello (ORLCCC) del Hospital Morales Meseguer (HMM) de Murcia y del Hospital Virgen del Castillo (HVC) de Yecla durante el periodo de estado de alarma debido a la COVID-19 y analizar los resultados obtenidos para valorar la utilidad de la consulta telefónica en nuestra especialidad.Material y métodosDesde el día 16 de marzo en los servicios de ORLCCC de los hospitales HMM y HVC comenzamos a realizar la consulta de forma telefónica. Debido a la disparidad de actuación de los diferentes miembros de los servicios se decidió realizar un protocolo para la gestión de dichas consultas que se comenzó a aplicar el 23 de marzo.ResultadosDurante el periodo de estudio en las consultas de ambos servicios se atendieron 1.054 pacientes, de los cuales 663 (62,9%) fueron primeras visitas y 391 (37,10%) fueron visitas sucesivas. El 21,73% (229) de las consultas se pudieron resolver de forma telefónica, el 10,82% (114) precisaron atención de forma presencial, al 57,40% (605) se les indicó revisión a demanda según la evolución de su patología y el 10,05% (106) de los pacientes no se pudieron localizar de forma telefónica.DiscusiónLa situación de estado de alarma ocasionada por la COVID-19 ha supuesto un condicionante en el desempeño de nuestra labor asistencial. En los servicios ORLCCC de los hospitales HMM y HVC decidimos realizar la consulta de forma telefónica como alternativa a la consulta tradicional. Durante este periodo hemos observado que hasta el 21,73% de las consultas se pudieron solventar de forma telefónica.ConclusiónLa consulta telefónica parece una herramienta muy útil para atender a nuestros pacientes evitando el riesgo de contagio por COVID-19 durante el estado de alarma. Además, según los datos analizados y los diferentes estudios, parece una buena alternativa a la consulta tradicional en pacientes seleccionados. (AU)

Objective: To describe how the ENT and Head and Neck departments of the HMM and HVC hospitals were managed during the COVID-19 state of alert and to analyse the results obtained to assess the usefulness of telephone consultations in our specialty.Material and methodsFrom March 16, the ENT and Head and Neck departments of the HMM and HVC Hospitals began telephone consultations. Due to the disparity in the actions of the different department members, the decision was made to create a protocol to manage these consultations which started to be implemented March 23.ResultsDuring the study period, 1054 patients were attended in the consultations of both departments; 663 (62.9%) were first visits and 391 (37.10%) were successive visits. Twenty-one percent (229) of the consultations could be resolved by telephone, 10.82% (114) required face-to-face care, 57.40% (605) were indicated for an on-demand check-up depending on their disease course, and 10.05% (106) of the patients could not be reached by telephone.DiscussionThe state of alarm caused by COVID-19 has been a determining factor in how we undertake our care work. In the ENT and Head and Neck departments of the HMM and HVC Hospitals we decided to carry out consultations by telephone as an alternative to the traditional consultation. During this period, we have observed that up to 21.73% of the consultations could be dealt with by telephone.ConclusionThe telephone consultation seems to be a very useful tool to attend our patients avoiding the risk of COVID-19 infection during the state of alarm. Furthermore, according to the data analysed and the different studies, it seems a good alternative to the traditional consultation in selected patients. (AU)

Structurally silent peptide anchor modifications allosterically modulate T cell recognition in a receptor-dependent manner.

Presentation of peptides by class I MHC proteins underlies T cell immune responses to pathogens and cancer. The association between peptide binding affinity and immunogenicity has led to the engineering of modified peptides with improved MHC binding, with the hope that these peptides would be useful for eliciting cross-reactive immune responses directed toward their weak binding, unmodified counterparts. Increasing evidence, however, indicates that T cell receptors (TCRs) can perceive such anchor-modified peptides differently than wild-type (WT) peptides, although the scope of discrimination is unclear. We show here that even modifications at primary anchors that have no discernible structural impact can lead to substantially stronger or weaker T cell recognition depending on the TCR. Surprisingly, the effect of peptide anchor modification can be sensed by a TCR at regions distant from the site of modification, indicating a through-protein mechanism in which the anchor residue serves as an allosteric modulator for TCR binding. Our findings emphasize caution in the use and interpretation of results from anchor-modified peptides and have implications for how anchor modifications are accounted for in other circumstances, such as predicting the immunogenicity of tumor neoantigens. Our data also highlight an important need to better understand the highly tunable dynamic nature of class I MHC proteins and the impact this has on various forms of immune recognition.

Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: an autopsy study with clinical correlation and review of the literature.

Pulmonary megakaryocytes participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are not mentioned as a characteristic histologic finding associated to pulmonary injury, a few studies reveal that their number is increased in diffuse alveolar damage (DAD). In this autopsy study, we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute lung injury (7.61 ± 5.59 megakaryocytes per 25 high-power fields vs. 1.14 ± 0.86 for the control group, p < 0.05). We analyzed samples of 18 patients, most of whom died after prolonged disease and use of mechanical ventilation. Most patients showed advanced DAD and abnormal coagulation parameters with high levels of fibrinogen, D-dimers, and variable thrombocytopenia. For comparison, pulmonary samples from a group of 14 non-COVID-19 patients dying with DAD were reviewed. They showed similar pulmonary histopathologic findings and an increase in the number of megakaryocytes (4 ± 4.17 vs. 1.14 ± 0.86 for the control group, p < 0.05). Megakaryocyte count in the COVID-19 group was greater but did not reach statistical significance (7.61 ± 5.59 vs. 4 ± 4.17, p = 0.063). Regardless of the cause, pulmonary megakaryocytes are increased in patients with DAD. Their high number seen in COVID-19 patients suggests a relation with the thrombotic events so often seen these patients. Since the lung is considered an active site of megakaryopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response.

Management of the ENT consultation during the COVID-19 pandemic alert. Are ENT telephone consultations useful? / Gestión de la consulta de otorrinolaringología durante el estado de alarma por la pandemia del COVID-19. ¿Es útil la consulta telefónica en ORL?

OBJECTIVE: To describe how the ENT and Head and Neck departments of the HMM and HVC hospitals were managed during the COVID-19 state of alert and to analyse the results obtained to assess the usefulness of telephone consultations in our specialty. MATERIAL AND METHODS: From March 16, the ENT and Head and Neck departments of the HMM and HVC Hospitals began telephone consultations. Due to the disparity in the actions of the different department members, the decision was made to create a protocol to manage these consultations which started to be implemented March 23. RESULTS: During the study period, 1054 patients were attended in the consultations of both departments; 663 (62.9%) were first visits and 391 (37.10%) were successive visits. Twenty-one percent (229) of the consultations could be resolved by telephone, 10.82% (114) required face-to-face care, 57.40% (605) were indicated for an on-demand check-up depending on their disease course, and 10.05% (106) of the patients could not be reached by telephone. DISCUSSION: The state of alarm caused by COVID-19 has been a determining factor in how we undertake our care work. In the ENT and Head and Neck departments of the HMM and HVC Hospitals we decided to carry out consultations by telephone as an alternative to the traditional consultation. During this period, we have observed that up to 21.73% of the consultations could be dealt with by telephone. CONCLUSION: The telephone consultation seems to be a very useful tool to attend our patients avoiding the risk of COVID-19 infection during the state of alarm. Furthermore, according to the data analysed and the different studies, it seems a good alternative to the traditional consultation in selected patients.

[Management of the ENT consultation during the COVID-19 pandemic alert. Are ENT telephone consultations useful?] / Gestión de la consulta de otorrinolaringología durante el estado de alarma por la pandemia del COVID-19. ¿Es útil la consulta telefónica en ORL?

Objective: To describe how the ENT and Head and Neck departments of the HMM and HVC hospitals were managed during the COVID-19 state of alert and to analyse the results obtained to assess the usefulness of telephone consultations in our specialty. Material and methods: From March 16, the ENT and Head and Neck departments of the HMM and HVC Hospitals began telephone consultations. Due to the disparity in the actions of the different department members, the decision was made to create a protocol to manage these consultations which started to be implemented March 23. Results: During the study period, 1054 patients were attended in the consultations of both departments; 663 (62.9%) were first visits and 391 (37.10%) were successive visits. Twenty-one percent (229) of the consultations could be resolved by telephone, 10.82% (114) required face-to-face care, 57.40% (605) were indicated for an on-demand check-up depending on their disease course, and 10.05% (106) of the patients could not be reached by telephone. Discussion: The state of alarm caused by COVID-19 has been a determining factor in how we undertake our care work. In the ENT and Head and Neck departments of the HMM and HVC Hospitals we decided to carry out consultations by telephone as an alternative to the traditional consultation. During this period, we have observed that up to 21.73% of the consultations could be dealt with by telephone. Conclusion: The telephone consultation seems to be a very useful tool to attend our patients avoiding the risk of COVID-19 infection during the state of alarm. Furthermore, according to the data analysed and the different studies, it seems a good alternative to the traditional consultation in selected patients.